Yeh Chun-Nan, Pang See-Tong, Chen Tsung-Wen, Wu Ren-Ching, Weng Wen-Hui, Chen Miin-Fu
Department of Surgery, Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan, ROC.
BMC Cancer. 2009 Jul 15;9:233. doi: 10.1186/1471-2407-9-233.
Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy
Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.
HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.
Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.
肝细胞癌（HCC）是全球第五大常见恶性肿瘤，是男性癌症相关死亡的主要原因，在台湾是女性癌症相关死亡的第二大原因。肝硬化和HCC相对普遍，台湾80%至85%的这些疾病患者乙肝表面抗原检测呈阳性。仅5%的普通人群所有乙肝病毒（HBV）标志物血清学呈阴性。这是第一项确定埃兹蛋白在HBV HCC细胞及接受肝切除术的HBV HCC患者中作用的研究。
对104例人类HBV-HCC病例进行埃兹蛋白免疫组化研究，以调查其与临床病理特征的相关性以及104例接受肝切除术的HBV-HCC患者的预后。此外，将包括野生型埃兹蛋白（wt-埃兹蛋白）和突变型埃兹蛋白Tyr353（Y353）的DNA构建体转染到Hep3B细胞中，以研究其在肿瘤侵袭和分化中的作用。
埃兹蛋白过表达的HBV HCC患者独立存在肿瘤体积较小、肝硬化肝背景、肿瘤分化差和更多血管侵犯的情况。埃兹蛋白表达状态对接受肝切除术的HBV-HCC患者的生存无影响。体外试验表明，与对照和Y353-埃兹蛋白Hep3B细胞相比，wt-埃兹蛋白Hep3B细胞的甲胎蛋白分泌水平显著更高，侵袭能力更强。
埃兹蛋白过表达促进了HBV-HCC细胞的去分化和侵袭。埃兹蛋白过表达的HBV-HCC患者独立与肿瘤体积较小、肝硬化肝背景、分化差和血管侵犯相关。
